immuno-Antigens
Terms
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- What is an Antigen (Ag)?
- is anything foreign to the body
- Autoantigen
- a self Ag (autologous)BAD- autoimmune disease
- Alloantigen
-
an antigenic difference within a speices (allogeneic)
e.g., kidney transplant - Xenoantigen
-
an antigenic difference between species (xenogeneic)
e.g., pig heart - Immunogenic
- An antigen that causes an immune response
- Haptens
-
small molecules that are antigenic but not immunogenic.
Need to be attached to a carrier to become immunogenic - Effectiveness of macromolecules as Ag
-
Proteins are often the most potent immunogens (only thing that can stimulate a T cell, best at B cells)
Polysaccharides are second (can stimulate B cells)
Lipids and nucleic acids are usually not immunogenic - What makes a good Ag?
- More foreign, bigger, more complex.
- Th1
- activate T cells, CMR
- Th2
- (Activate B cells, HMR)
- role of genetics in antigen response
- Genetics determines whether one will respond with T helper 1 response, activating T cells and inducing a cell mediated response or T helper 2 which activates B cells and induces a Ab response. In addition if one doesn’t have the MHC (HLA) for a particular Ag, it will not induce an immune response. Similary, if one is lacking a B cell receptor (BCR) or T cell receptor (TCR) to an Ag there will also be no response.
- Relatively high and low doses are usually not immunogenic
- low doses are thought by the immune system to not be significant to engage a response. High doses indicate to the immune system that it might be self because there is so much of it.
- Route plays a role in immune response
- intermuscular is better to produce a response because generally stays around longer.
- Proteins
- best antigenic bio-organic molecule
- multideterminate Ag
- multiple sites on molecule that can be regognized by antibody
- Epitope
-
-Area that is recognized on Ag
-T cell epitopes are on inside of Ag
-B cell epitopes are on outside of Ag - B cell epitopes
-
-external epitopes
-can be sequential or non-sequential (conformational)
For proteins, ~8 – 22 a.a. interact with Ab - T cell epitopes
-
– epitopes can be anywhere in protein
-are sequential
-Between 8-10 a.a (CD8+) and 13-18 a.a. (CD4+)
constraints by MHC binding groove
Ag must interact with TCR AND MHC
Ag must “fit†in binding groove of the MHC - For a given protein Ag, there can be _______ T and B cell epitopes
- multiple
- epitopes can be ________
- overlapping
- some epitopes are __________
- immunodominant
- immunodominant epitopes
- ones best at stimulating immune response
- Types of immunogenic molecules
-
Starts a non-antigen specific activator of T or B cells which causes proliferation and then death
e.g. LPS non-specifically activates B cells so that they die out prematurely
Concanavalin A (ConA) non-specifically activates T cells so that they die out prematurely - T-independent (TI) Ags
-
-Response does not require T cells
-B cell response
-no memory cells - T dependent (TD) Ags (BEST)
- -Response requires T cell help (cytokines); T cell stimulation provides best immune response because produces memory cells
- Haptens need T cell help for immunogenicity
- if you bind hapten to protein carrier you can get secondary immune memory response to both bound hapten and bound carrier
- Specificity of the immune response
-
The immune system can recognize slight differences in an antigen
e.g., recognizes difference between o,m,p aminobenzene -
Usually, immune system is very specific but ________ do occur because non-related molecules can share ______.
This can result in _______ - Cross-reactions, epitopes,autoimmunity
- Adjuvants
-
Adjuvants are compounds that when mixed with immunogens, makes them more immunogenic
equals stronger immune response
e.g., oils or oil bases that make antigen stay around longer